Regulation of glycogen synthase activity in the isolated mouse soleus muscle. Effect of insulin, epinephrine, glucose and anti-insulin receptor antibodies.
The effects of insulin, epinephrine, glucose and anti-insulin receptor antibodies on enzymes involved in the regulation of glycogen synthesis were investigated in the isolated mouse soleus muscle. Insulin maximally increased the percentage of glycogen synthase active form after 15 min in the absence of glucose in the extracellular medium; half-maximal and maximal effects were obtained with 1.5 and 33 mM insulin, respectively. The basal percentage of glycogen phosphorylase active form was not altered by insulin. Antibodies to the insulin receptor had similar effects to those of insulin on both enzymes. The percentage of glycogen synthase active form was maximally decreased and that of phosphorylase maximally increased after a 2 min exposure to epinephrine in the absence of extracellular glucose. Glucose alone had no effect on muscle glycogen synthase. When muscles were incubated with insulin (33 nM) plus glucose (20 mM) for 5-10 min, the increase in the percentage of glycogen synthase active form was greater than with insulin alone. This enhancing effect of glucose on insulin activation of glycogen synthase disappeared after 20 min. The results suggest the existence of two mechanisms whereby insulin activates muscle glycogen synthase. The main effect is operative in the absence of extracellular glucose and occurs at insulin concentrations close to the physiological range. The other effect requires glucose and may result from the stimulation by insulin of glucose transport and/or metabolism.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009132:Muscles / Q000201:enzymology*; D010695:Phlorhizin / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism; D011972:Receptor, Insulin / Q000276:immunology*
D001323:Autoantibodies; D007328:Insulin; D010695:Phlorhizin; D006005:Phosphorylases; D006006:Glycogen Synthase; D011972:Receptor, Insulin; D005947:Glucose; D004837:Epinephrine